This grant has enabled the development of a unique antiviral agent, 5-iodo-5'-amino-2',5'-dideoxyuridine (AIU; AIdUrd) which because it is only activated by a viral encoded enzyme has good antiviral activity in vitro and in vivo with no host toxicity. The objectives are to synthesize additional novel antiviral and anticancer nucleoside analogues, to evaluate their spectra of biological activity, and to determine the site of inhibition and mechanism of action of those compounds which have good inhibitory activity. Both antiviral and anticancer activities are evaluated initially in cell culture, and then in animal systems using a variety of virus infections as well as a number of transplanted neoplasms.